When it comes to PCSK9s, payers resisted — and sales flopped

A handful of anticipated branded products that gained FDA approval in the generics-dominated cardiovascular disease space have garnered barely audible post-launch applause. These treatments, both novel ones and me-toos, are being met with payer resistance, prescriber uncertainty, and pricing problems.

As attention increasingly shifts to the enormous need — and tremendous ROI — in the autoimmune and oncology sectors, the development of CV drugs has fallen out of favor, even as heart disease and stroke remain top killers in the U.S. The sector is predicted to rise — albeit at a comparatively low rate — but will likely weather significant shifts as several category stars are stripped of patent protection.

See also: Top 25 cardiovascular brands, 2015-2016

Although the pipeline for heart medications is showing signs of rejuvenation, industry forces may have forever changed the market in which these drugs aim for approval. According to Gil Bashe, managing partner of health at Finn Partners, value-based pricing is driving the disparity between disease statistics and drug development. “The opportunity to address heart disease remains high,” he notes. “Payers are balancing the value of the science and the value of a drug's impact on patient care and cost.”

The price of marketed products has emerged as a major influencing factor in the launch — and the development — of new treatment solutions. This played out publicly over the past 18 months with the lackluster launches of Sanofi/Regeneron's Praluent (alirocumab) and Amgen's Repatha (evolocumab). Both drugs are PCSK9 inhibitors, a new class of drugs approved for patients with severe hyperlipidemia and a narrow subset of patients at high risk for cardiovascular disease who are unable to control LDL cholesterol through diet or high doses of statins.

But a court ruling in January puts that competition in question. A judge ordered Sanofi and Regeneron to stop marketing Praluent for 12 years, citing Amgen's claim that the therapy violates Amgen's patents for Repatha. Sanofi and Regeneron have said they will appeal the injunction. 



PRICE TAG PROBLEMS

In the 18 months since Praluent and Repatha received the FDA's stamp of approval, payers have erected reimbursement walls in response to sky-high price tags that stand in stark contrast with the largely generic statin class. The pricing wedge may drive even deeper when statin leaders, including AstraZeneca's Crestor (rosuvastatin) and Merck's Zetia (ezetimibe) and Vytorin (ezetimibe/simvastatin), begin to face generic competition.

Although initially approved for a limited patient segment, PCSK9s were earmarked to quickly penetrate a broader swath of patients with heart disease. Many await the results of several large outcomes trials due later this year, with data expected to seal a foundation of support for expanded use of the drugs. In the meantime, many marketers have speculated about why the scripts haven't begun to pile up.

One obvious issue is the hefty price tag hanging on the boxes of PCSK9 inhibitors: roughly $14,000 annually. Even with revolutionary supporting science alongside generic statins, it's hard for payers to embrace drugs at this price.

“Payers don't feel compelled to open the door to access and their checkbooks to preferred formulary status,” Bashe says.

Pricing debates are making drug developers think twice about the future marketability of pipeline products — those steering toward preclinical examination, as well as those in late-stage development. “It's a big issue,” stresses DalCor Pharmaceuticals CEO Robert McNeil. “The industry needs to consider the cost of drugs.”

But to some, there's nothing amiss. Dr. Paul Thompson, director of cardiology at Hartford Hospital and a member of the American College of Cardiology's sports and exercise council, believes there are no signs of a slow PCSK9 uptake.

“As prescribers, we have a responsibility to not overprescribe until we have the information we need,” he argues. “What will happen when control trials confirm what we think? The dam will open.”

On the flip side, even if the outcomes data show a true benefit associated with PCSK9 inhibitors, Megan Doyle, Ph.D., scientific director at Discovery USA, predicts payers will continue to use as many tools as possible to restrict access to patients within FDA labeling. In the interim, she cautions marketers to temper the expectation of changing practice patterns overnight.

Marianne Andreach, SVP of strategic marketing and product planning at Esperion Therapeutics, says PCSK9 inhibitor launches are reminiscent of the debut of statins in the late 1980s — though, she admits, the price issue is absent from the parallel. “Before statins gained any level of traction, there was a high degree of skepticism about the approach,” she recalls.



ROOM FOR NEW PLAYERS

Due to overwhelming positive data, statins are now the most prescribed drug class worldwide. As a result, companies lost interest in investing in new approaches to lowering cholesterol.

“The improvement curves have leveled off now, and we're not doing enough,” Andreach continues. “Statins are wonderful drugs. But for patients with type 2 diabetes and other co-morbidities, the optimal management is more than one drug.”

Esperion president and CEO Tim Mayleben adds physicians and patients often express the need for more LDL-lowering therapeutic options, in particular oral options. Due to intolerance issues, statins leave nearly 12 million U.S. patients short of their treatment goals.

See also: For statin-intolerant patients, what's next?

These factors leave an open door for the uptake of PCSK9 inhibitors and other solutions. Esperion's bempedoic acid, an oral cholesterol-lowering treatment in Phase III trials, is angling to be one such drug.

A new class of novel oral anticoagulants (NOACs), including Boehringer Ingelheim's Pradaxa (dabigatran etexilate), Janssen's Xarelto (rivaroxaban), and Bristol-Myers Squibb's Eliquis (apixaban), is gaining ground on generic warfarin blood thinners, the category's mainstay. Warfarin comes out a winner on the price-comparison front, but subjects patients to onerous monitoring and food and drug interactions.

In these times of upheaval, medical devices and drug-device combos are not immune to indifferent market debuts, but reports show signs they could reign supreme. Evaluate-MedTech experts predict annual sales of cardiology-related devices will reach $62.3 billion by 2020, a 48% leap over 2015 sales of $42.1 billion.

Drug-device combos, a phenomenon launched in 2003 with Johnson & Johnson's Cypher stent, blur the lines between pharma and med-tech.

See also: BI and Lilly face a new challenge: how to market a diabetes drug to cardiologists

“While the number of pure cardiovascular drugs has plummeted in the past two decades, the number of drug-coated devices seems to be rising,” says Pamela Froneberger, director, FTI Consulting. She points to medical device manufacturers extending drug-coating technology to coronary balloons and pacing leads.

Meanwhile, another drug category is angling for a resuscitation. In a bold move based on genetic variation, DalCor plucked CETP inhibitor dalcetrapib from Roche's discard pile following a failed Phase III study in nearly 16,000 patients. It plans to run its own 5,000-person trial. If successful, the drug's approval would be unprecedented.

McNeil believes targeting patients with a particular genomic composition could generate a dramatic improvement for the cardio sector. Drawing a parallel between dalcetrapib and Roche's Herceptin — which works with one segment of breast cancer patients — he predicts the field of genetics will unlock new avenues in cardiology, just as it has in oncology.

“Humans have different backgrounds and genetics, and that means our responsiveness to drugs is different,” he notes.



MIXED REACTIONS

Owing to the increasing global population of seniors, the pool of patients with cardiovascular conditions is growing fast. As a result, marketers are exploring whether raising cardiovascular disease awareness through educational resources and ads can impact medication compliance and lifestyle influences.

As part of an effort to encourage Americans to take charge of their health, Amgen launched the multi-tiered Breakaway from Heart Disease campaign. It includes an educational website, social media outreach, and disease awareness TV spots featuring NFL Hall of Famer Joe Montana — who was diagnosed with high cholesterol and high blood pressure — discussing the merits of effecting lifestyle changes to improve heart health.

Unlike in many other areas of medicine, lifestyle and diet changes contribute significantly to the pathophysiology of cardiovascular disease.

See also: GSW's Erik Slangerup on Ads with Heart

“New drugs need to become part of a multi-pronged program of care that includes improved patient education, long-term monitoring, and multiple providers,” says Jennifer Lilla, Ph.D., CardioVascular Resource Group's therapy area director.

But not everyone agrees with the messages drug companies are sending. Novartis found itself on the receiving end of backlash for a disease-awareness ad that was seen as dark and disturbing — more a scare tactic than an education push. Proponents of the approach countered the serious nature of the disease warranted a to-the-point message. Though timed to accompany the launch of HF drug Entresto, the product was not even mentioned in the ad.

In the end, today's complex landscape may prove a significant barrier to drug development, especially for novel mechanisms facing a high safety bar for long-term use. Drugs like Entresto have struggled to gain a foothold in well-served areas, likely due to its prohibitive cost. As a result, Entresto's Q1 2016 U.S. sales of just $17 million failed to impress. Many wonder if Novartis' decision to sink $200 million into marketing efforts will pay off in the end.

In response to the brewing pricing superstorm, Novartis CEO Joe Jimenez inked a value-based pricing deal with insurers for Entresto. It's a step in the right direction amid demands that manufacturers justify prices to steer the conversation toward outcomes.